When a patient begins taking an agent or combination of agents or any medication(s) for a length of time, a titration of the amount of agent(s) taken by the patient is necessary in order to achieve the optimal benefit of the agent(s), and at the same time to prevent any undesirable side effects that taking too much of the agent(s) could produce. Thus, there is a continuous balance between taking enough of the agent(s) in order to gain the benefits from that agent(s), and at the same time not taking so much agent(s) as to elicit a toxic event.
There is large inter-individual variability in the patient biological interactions and/or the patient pharmacodynamic and pharmacokinetic interactions of agents. What may be an appropriate agent dose for one individual may be too much or too little for another. A physician referring to the product insert is required to estimate the correct agent dosage for a patient and then to experiment with that dosage, usually by trial and error, until the correct dosage is achieved. Likewise, the FDA labeling of an agent suggests dosages based on epidemiological studies and again does not account for inter-individual variability. Non-linear least squares modeling methods involve the use of large amounts of data relating to a general population in order to calculate a best fit. Much like linear regression models, this method cannot take into account the variability between people with the same population characteristics.
Bayesian analysis is another method used to relate agent dose to efficacy. This method employs large-scale population parameters to stratify a population in order to better characterize the individuals. This method does not take into account the changes that can occur within a person over time, and as a result cannot reliably estimate dosages.
Pharmacokinetic compartment modeling has had success with some agents, but because the models are static and cannot adapt themselves to changes within a population or a patient, they are once again undesirable for dynamically determining agent dosages.
Expert systems have been developed by this applicant using similar technology to predict drug dosages for immunosuppressant drugs (U.S. Pat. Nos. 5,365,948; 5,542,436 and 5,694,950). These algorithms however were not generic and only use immunosuppressant blood levels. Each algorithm is specific to an individual immunosuppressant drug. As it stands, these inventions cannot be applied to other drugs. A more recent dosing system, the IDS™ has been developed (U.S. Pat. No. 6,267,116 B1) that is generic but does not take into account the level or degree of response that a patient has. Some biological markers cannot be pushed beyond certain limits such as the INR, blood pressure or glucose levels. This system (U.S. Pat. No. 6,267,116 B1) also only produces a single next dose as its calculation. The system being described produces the range of doses necessary to achieve the desired response, plus or minus 5%. This is clinically much more relevant to the physicians treating their patients. This model also requires a separate embodiment for the percentage of surrogate markers embodiment that is not required in this new model. Previous dosing models put forth by the applicant assumed that the degree of nonlinearity continually increased over the dosing range. These models did not take into account the saturation effect that high doses of drug exhibit, that is where the degree of nonlinearity begins to decrease at the highest end of the dosing range. Saturation of response occurs as more and more drug is added to a system. While more drug elicits a larger effect, at very high doses the effect is lessened due to the inability to push biological markers beyond certain limits. The dosing model set out in this application more accurately describes and takes into account the saturation effect as it relates to the biological process of dose titration.
Applicant's U.S. Pat. No. 6,267,116 discloses a major breakthrough in IDS™ technology, but can only accommodate one drug at a time and is inferior dosing technology for the reasons described above.
It is a desideratum of the present invention to avoid the animadversions of conventional systems and techniques.